Nicolai Cramer

Cyclobutanes in catalysis.

The exploitation of ring strain as a driving force to facilitate chemical reactions is a well-appreciated principle in organic chemistry. The most prominent and most frequently used compound classes in this respect are oxiranes and cyclopropanes. For rather a long time, cyclobutanes lagged behind these three-membered-ring compounds in their development as reactive substrates, but during the past decade an increasing number of useful reactions of four-membered-ring substrates have emerged. This Minireview examines corresponding catalytic reactions ranging from Lewis or Brønsted acid catalyzed processes to enzymatic reactions. The main focus is placed on transition-metal-catalyzed C-C bond-insertion and β-carbon-elimination processes, which enable exciting downstream reactions that deliver versatile building blocks.

Chiral Cyclopentadienyl Ligands as Stereocontrolling Element in Asymmetric C–H Functionalization

Forced Asymmetry in Cp The cyclopentadienyl (Cp) ligand—a pentagon of carbons—is a common feature in transition metal catalysts, but chiral variants of the structure have rarely been applied to asymmetric reactions. Two studies now demonstrate distinct approaches to rendering a Cp-derived rhodium catalyst enantioselective in a tandem carbon-hydrogen activation-ring closure reaction that couples olefins with benzamides (see the Perspective by Wang and Glorius). Hyster et al. (p. 500) tethered a biotin derivative to the Cp ligand to enable docking in a chiral streptavidin protein cavity, which in turn was engineered to further optimize catalytic performance. Ye and Cramer (p. 504) appended chiral substituents on the Cp framework to bias the rest of the coordination environment around the metal center. A ligand rarely applied to asymmetric catalysis has been chirally modified to furnish a highly selective rhodium catalyst. Metal complexes coordinated by a single cyclopentadienyl (Cp) ligand are widely used, versatile catalysts, but their application to asymmetric reactions has been hindered by the difficulty of designing Cp substituents that effectively bias the coordination sphere. Here, we report on a class of simple C2-symmetric Cp derivatives that finely control the spatial arrangement of the transiently coordinated reactants around the central metal atom. Rhodium(III) complexes bearing these ligands proved to be highly enantioselective catalysts for directed carbon-hydrogen (C–H) bond functionalizations of hydroxamic acid derivatives.

Catalytic C-C Bond Activations via Oxidative Addition to Transition Metals.

Selective cleavages of carbon-carbon bonds catalyzed by transition-metal complexes have been shown to be increasingly versatile tools for organic synthesis allowing for complementary synthetic strategies. Numerous examples of transition-metal catalyzed C-C bond activations of three- and four-membered ring systems have been reported. These strained rings have been shown to engage in a variety of new ring-opening rearrangements and cycloaddition reactions leading to valuable structures. Besides strain-driven transformations, other facilitating strategies to enforce the C-C bond activation of unstrained molecules have been developed as well. While the variety of different transformations is less abundant, they concentrate on chelation-assisted reactions using appropriate permanent or transient directing groups. In particular, the cleavage and subsequent functionalization of the C-CN bonds and decarbonylation processes operating by an excision of carbon monoxide from ketone derivatives have witnessed a large progress.

A Tunable Class of Chiral Cp Ligands for Enantioselective Rhodium(III)-Catalyzed C–H Allylations of Benzamides

The lack of robust and tunable chiral versions of cyclopentadienyl (Cp) ligands hampers progress in the development of catalytic asymmetric versions of a myriad of reactions catalyzed by this ubiquitous ligand. Herein, we describe of a class of chiral Cp ligands with tunable steric parameters. Coordinated to transition metals, the ligand creates a well-defined chiral pocket, able to imprint its chirality onto the metal. The corresponding Rh complexes are shown to be excellent catalysts for enantioselective allylation of N-methoxybenzamides via directed C-H functionalizations at very mild conditions. The obtained enantioselectivities are excellent and demonstrate the viability of chiral Cp complexes as selective transition metal catalysts.

Enantioselective Synthesis of Indanols from tert-Cyclobutanols Using a Rhodium-Catalyzed C-C/C-H Activation Sequence

Tert.-Cyclobutanols were activated through an enantioselective rhodium(I)-catalyzed insertion into the C-C bond leading to arylrhodium species. These intermediates are converted by a C-H activation mechanism to arylrhodium species that are converted to indanol derivs. in stereoselective manner.

Rhodium-catalyzed C-C bond cleavage: construction of acyclic methyl substituted quaternary stereogenic centers.

A rhodium-catalyzed enantioselective insertion into the C-C bond of tert-cyclobutanols and subsequent proto-demetalation provides access to methyl substituted quaternary stereogenic centers in excellent yields and enantioselectivities. The reaction was used for a synthesis of (S)-4-ethyl-4-methyl-octane, the simplest saturated hydrocarbon with a quaternary stereogenic center.

Access to Sultams by Rhodium(III)‐Catalyzed Directed CH Activation

Directors cut: The pharmaceutically relevant sulfonamide group is shown to be a competent directing group for [Cp*Rh(OAc)(2)]-catalyzed C-H functionalizations. Reactions of the cyclometalated intermediate with internal alkynes provide access to a wide range of sultam derivatives. The reaction is high yielding and works best under aerobic conditions with catalytic amounts of CuOAc as an oxidation mediator. Cp* = C(5)Me(5).

Chiral Monodentate Phosphines and Bulky Carboxylic Acids: Cooperative Effects in Palladium‐Catalyzed Enantioselective C(sp3)–H Functionalization

Keywords: asymmetric catalysis ; C?H activation ; cooperative effects ; palladium ; phosphines ; C-H Activation ; Quaternary Stereogenic Centers ; Intramolecular Alkane Arylation ; Unactivated C(Sp(3))-H Bonds ; Asymmetric Hydrogenation ; Mild Conditions ; Methyl-Groups ; Ligands ; Derivatives ; Indolines Reference EPFL-ARTICLE-176461doi:10.1002/anie.201108511View record in Web of Science Record created on 2012-04-26, modified on 2017-12-03

syn-Selective Rhodium(I)-Catalyzed Allylations of Ketimines Proceeding through a Directed CH Activation/Allene Addition Sequence†

Rhodium(I)-catalyzed C-H functionalization of aryl ketimines and subsequent carborhodation of a terminal allene resulted in the formation of allyl rhodium intermediates, which underwent allylation of the imine to give cyclized products, e.g., I, with high regioselectivity and diastereoselectivity. Preliminary attempts to develop an enantioselective variant were also successful.

Enantioselective metal-catalyzed activation of strained rings

Activation of otherwise inert bonds has significant potential in the design of efficient and synthetically useful transformations. While general catalytic carbon-carbon single bond activations are still in their infancy, this emerging area examines recent developments in the activation of strained rings, focusing on enantioselective reactions.